This is a proposal for support of the Second Workshop on Folyl and Antifolyl Polyglutamates to be held at the Airlie Conference Center in Airlie, Virginia, November 14 thru 17, 1984. This research area has broad biochemical and pharmacologic importance and involves a class of anticancer drugs, the 4-amino-antifolates and related compounds that are of particular interest to the Division of Cancer Treatment. Over the past five to six years considerable progress has been made in the understanding of the importance of folylpolyglutamates in folate-dependent biosynthetic processes. These compounds are now recognized as the biologically important tetrahydrofolate cofactors. Of particular recent interest is the increasing awareness of polyglutamyl derivatives of 4-amino-antifolates as critical determinants of the cytotoxicity and selectivity of this class of agents. The proposed conference will involve all key investigators in this research area and will touch upon all of the major areas of progress that have been made since the last workshop was held in May, 1981 at the Airlie Conference Center. The program encompasses the important chemical, biochemical and pharmacologic issues that will require further intensive scientific exploration.